Cyclization of hydrazones of 2-acetyl-1-naphthol and 1-Acetyl-2-naphthol with triphosgene. Synthesis of spiro naphthoxazine dimers

Article abstract of DOI:10.3390/molecules14062147

Cyclization of hydrazones derived from 2-acetyl-1-naphthol and 1-acetyl-2-naphthol with triphosgene gave naphtho[1,2-e]-1,3-oxazines, naphtho[2,1-e]-1,3-oxazines or their spiro dimers depending on the molar ratio of triphosgene used for the cyclization.

Full text of DOI:10.3390/molecules14062147

Molecules 2009, 14, 2147-2159; doi:10.3390/molecules14062147
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Cyclization of Hydrazones of 2-Acetyl-1-naphthol and 1-Acetyl-
2-naphthol with Triphosgene. Synthesis of Spiro Naphthoxazine
Dimers
Abdullah Saad Al-Bogami 1, Abdullah Mohammed Al-Majid 1, Mohammed Ali Al-Saad 1,
Ahmed Amine Mousa 1, Sara Abdullah Al-Mazroa 2 and Hamad Zaid Alkhathlan 1,*
1
Department of Chemistry, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia
2
Chemistry Department, Girls College of Education, Riyadh Girls University, Riyadh, Saudi Arabia
* Author to whom correspondence should be addressed; E-mail: khathlan@ksu.edu.sa;
Tel: +966-1-4675910; Fax: +966-1-4675992
Received: 25 April 2009; in revised form: 15 May 2009 / Accepted: 5 June 2009 /
Published: 12 June 2009
Abstract: Cyclization of hydrazones derived from 2-acetyl-1-naphthol and 1-acetyl-2-
naphthol with triphosgene gave naphtho[1,2-e]-1,3-oxazines, naphtho[2,1-e]-1,3-oxazines
or their spiro dimers depending on the molar ratio of triphosgene used for the cyclization.
Keywords: 2-acetyl-1-naphthol; 1-acetyl-2-naphthol; triphosgene; naphthoxazine, spiro
naphthoxazine
Introduction
Triphosgene (bis(trichloromethyl)carbonate) has been repeatedly used in the literature for the
construction of a variety of heterocyclic systems. It holds an advantage over other similar reagents,
such as phosgene and diphosgene, of being a safe and easy to handle solid. Examples of important
heterocyclic systems prepared using this reagent include benzothiadiazepines [1], quinazolines [2],
diazolidines [3], imidiazolidines [4] and azetidines [5]. We have recently reported the use of
triphosgene in the cyclization of hydrazones and Schiff bases of 2-hydroxy- and 2-
aminoacetophenones to give 1,3-benzoxazines [6,7], spiro 1,3-benzoxazine dimmers [8], quinazolines
and spiro quinazoline dimers [9].

Molecules 2009, 14
2148
We would like to report here results obtained from the cyclization of hydrazones of 2-acetyl-1-
naphthol and 1-acetyl-2-naphthol with triphosgene.
Results and Discussion
Hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol were obtained in very good yields from
the reaction of these compounds with aromatic hydrazines (Scheme 1, Table 1).
Scheme 1. Synthesis of hydrazones of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol.
OH
N NHAr
OH
O
1-4
i
O
N
NHAr
OH
OH
5-8
i = ArNHNH2.HCl/EtOH/AcONa/H2O
Table 1. Hydrazones 1-8.
Compound
Ar
Phenyl
4-ClC6H4
4-BrC6H4
4-CH3C6H4
Phenyl
4-ClC6H4
4-BrC6H4
4-CH3C6H4
Yield (%)
1
2
3
4
5
6
7
8
92
82
79
91
75
80
68
68
The hydrazones 1-8 show in the their IR spectra absorbances for the C=N group in the 1,614-
1,636 cm-1 range and for the OH and NH groups at about 3,400 cm-1 and 3,350 cm-1, respectively. The
1H-NMR spectra of compounds 1-8 show in each case two distinct doublets which have been assigned
to the H3 and H4 positions. In the spectra of 1-4 these two doublets appear at  7.04-7.16 and
 7.68-7.76. The lower field signal in this case was assigned to H3 as it is deshielded by the hydrazone
moiety. In contrast, for compounds 5-8, where the two doublets appear at  6.80-6.90 and  7.63-7.66
the signal at the higher field was assigned to H3 as in this case this position is shielded by the OH
13
group. It is also worth mentioning here that in the C-NMR spectra of the above compounds, the
methyl group of the hydrazones of the 2-acetyl derivatives 1-4 absorbs at higher fields ( 12.22-13.04)

Molecules 2009, 14
2149
than those of the 1-acetyl derivatives 5-8 ( 18.29-18.55). The rest of the spectral data is shown in the
Experimental section. Treatment of the hydrazones 1-8 with triphosgene gave the
4-methylenenaphthoxazines 9-16 or the spiro naphthoxazine dimers 17-20, depending on the molar
ratio of triphosgene used in the cyclizations (Schemes 2 and 3, Table 2).
Scheme 2. Reaction of hydrazones 1-4 with triphosgene.
OH
N NHAr
1-4
(Cl3CO)2CO
1 eq.
0.5 eq.
9
10
O
8
7
2
3
N NHAr
1
O
1
O
O
2
10
10b
4
ArNH 3N
4
9
6
CH2
3'
N
5
Ar
2'
1'
8
5
4'
H3C
N
6
7
12'b
7'
5'
12'
O
9-12
11'
O6'
10'
9'
8'
17-19
Scheme 3. Reaction of hydrazones 5-8 with triphosgene.
N
NHAr
OH
5-8
(Cl3CO)2CO
1 eq.
O
0.5 eq.
NHAr
1
O
10
2
9
H2C
4
N
2
O
3
ArNH 3N
4
2'
5
8
7
O1
10a
3'
1'
6
7
N
5
Ar
4'
12' H3C
11'
9'
N
6
10
12'c
5'
O
10'
8
9
O6'
13-16
8'
7'
20

Molecules 2009, 14
Table 2. 4-Methylenenaphthoxazines 9-16 and spiro naphthoxazine dimmers 17-20.
2150
Compound
Ar
Phenyl
Yield (%)
69
9
10
11
12
13
14
15
16
17
18
19
20
4-ClC6H4
4-BrC6H4
4-CH3C6H4
Phenyl
4-ClC6H4
4-BrC6H4
4-CH3C6H4
Phenyl
74
71
73
62
61
64
60
69
4-ClC6H4
4-BrC6H4
4-CH3C6H4
72
71
55
These results are in agreement with our previous reports on the reaction of hydrazones of
2-hydroxyacetophenones with triphosgene. It was observed then that the use of 0.5 equivalents of
triphosgene gave the 4-methylene-1,3-benzoxazines, while the spiro 1,3-benzoxazine dimers were
obtained when 1.0 equivalent of triphosgene was used [8]. The structures of those compounds were
established based on X-ray crystal structure and spectroscopic studies [8,9]. As a result, we are
showing here partial spectroscopic data for compounds 9-16 (Tables 3 and 4) and 17-20 (Table 5). In
these tables, signals that can be easily attributed to structurally related positions, and with significance
to the elucidation of the structures of the new compounds are shown for matter of comparison, while
the complete data is given in the experimental section.
Table 3. Partial IR and NMR data for compounds 9-16.
IR (cm-1)
C=O =CH2
1H-NMR (ppm)
Compound
=CH2
Aromatic
9
1,727 1,620 5.02 (d, J = 2.2 Hz, 1H) 6.80 (d, J = 8.1 Hz, 2H, H2,6,Ar
)
5.13 (d, J = 2.2 Hz, 1H)
7.61 (d, J = 8.8 Hz, 1H, H6)
7.66 (d, J = 8.8 Hz, 1H, H5)
10
1,732 1,621 5.02 (d, J = 2.2 Hz,1H)
5.09 (d, J = 2.2 Hz, 1H)
6.78 (d, J = 9.0 Hz, 2H, H2,6,Ar
)
7.23 (d, J = 9.0 Hz,2H, H3,5,Ar
)
7.67 (d, J = 8.8 Hz, 1H, H5)
11
12
1,741 1,621 4.96 (d, J = 2.0 Hz, 1H) 6.73 (d, J = 8.8 Hz, 2H, H2,6,Ar)
5.01 (d, J = 2.0 Hz, 1H) 7.24 (d, J = 8.8 Hz, 2H, H3,5,Ar
)
1,737 1,612 4.92 (d, J = 2.0 Hz, 1H) 6.71 (d, J = 8.1 Hz, 2H, H2,6,Ar
5.14 (d, J = 2.0 Hz, 1H) 7.02 (d, J = 8.1 Hz, 2H, H3,5,Ar
7.84 (d, J = 8.8 Hz, 1H, H6)
)
)
7.91 (d, J = 8.8 Hz, 1H, H5)
13
1,725 1,620 5.04 (d, J = 2.2 Hz, 1H) 6.97 (d, J = 8.8 Hz, 2H, H2,6,Ar
)
5.15 (d, J = 2.2Hz, 1H)
7.67 (d, J = 8.1 Hz, 1H, H9)

Molecules 2009, 14
2151
Table 3. Cont.
14
1,732 1,620 5.05 (d, J = 1.5Hz, 1H)
6.84 (d, J = 8.8 Hz, 2H, H2,6,Ar
)
5.15 (d, J = 1.5 Hz, 1H) 7.23 (d, J = 8.8 Hz, 2H, H3,5,Ar
7.70 (d, J = 8.1 Hz, 1H, H9)
)
15
16
1,733 1,616 5.05 (d, J = 2.2 Hz, 1H) 6.90 (d, J = 8.0 Hz, 2H, H2,6,Ar
)
)
5.14 (d, J = 2.2 Hz, 1H) 7.29 (d, J = 8.0 Hz, 2H, H3,5,Ar
1,741 1,615 5.04 (d, J = 2.2 Hz, 1H)
6.81(d, J = 8.8 Hz, 2H, H2,6,Ar)
5.14 (d, J = 2.2 Hz, 1H) 7.08 (d, J = 8.8 Hz, 2H, H3,5,Ar
)
7.66 (d, J = 8.8 Hz, 1H, H9)
Table 4. Partial 13C-NMR data for 9-16.
9
10
11
12
13
14
15
16
C1,Ar
C2,6,Ar
C3,5,Ar
C2
143.05 143.46 143.35 143.34 143.53
113.03 115.70 114.89 113.07 113.97
129.30 132.33 131.99 130.03 129.45
148.05 147.99 147.35 147.21 148.07
138.69 138.26 138.54 138.99 138.46
143.48
115.33
129.44
148.01
138.30
88.53
143.53
113.96
129.47
148.08
138.45
88.54
142.88
114.12
129.96
148.10
138.48
88.50
C4
=CH2
C5 (C10)
C6 (C9)
C10b (C10a)
C2
88.60
88.55
88.58
88.97
88.53
122.93 121.48 121.52 121.50 (120.33) (120.25) (120.33) (120.34)
120.69 120.24 120.73 121.05 (128.12) (128.23) (128.13) (128.10)
146.16 144.45 145.60 144.14 (145.29) (143.95) (145.29) (143.53)
148.05 147.99 147.35 147.21 148.07
148.01
148.08
148.10
Table 5. Partial 1H and 13C-NMR data for the spiro compounds 17- 20.
1H
13C
C2`
CH3
2.12
C1`
CH3
C1`
C12`b
C=O
17
18
19
20
3.58 (d, J = 14.70 Hz, 1H)
3.69 (d, J = 14.70 Hz, 1H)
32.15
59.65
85.55
85.47
85.41
66.06
149.24
149.90
2.10
2.09
2.51
3.49 (d, J = 14.70 Hz, 1H)
3.60 (d, J = 14.70 Hz, 1H)
32.08
32.04
17.20
60.07
60.11
27.87
66.05
65.96
149.01
149.07
3.44 (d, J = 14.70 Hz, 1H)
3.54 (d, J = 14.70 Hz, 1H)
148.95
149.15
3.41 (d, J = 14.65 Hz, 1H)
3.54 (d, J = 14.65 Hz, 1H)
97.68 (88.06)* 148.60
149.01
*(C12'c).
13
It can be seen from Table 3 that there is a noticeable difference in the C-NMR spectra of 17-19
compared with 20. In the latter compound the CH3 group and position C1` absorb at higher fields than
those in 17-19, while positions C2` and C12`c absorb at lower fields than positions C2' and C12'b in 17-19.
This might be speculated as a result of the orientation of the aromatic rings in respect to these
positions, which needs further studies. In addition, the above results for compounds 17-19 are in close

Molecules 2009, 14
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resemblance to these reported for the spiro 1,3-benzoxazine dimmers which might suggest that they
have similar steric environment for the 1,3-benzoxazines[8].
The EIMS spectra of the spiro compounds 17-20 did not show the expected molecular ions. They
appear to fragment at the spiro junction to give fragments at m/z = M+ - ArN2CO and
m/z = M+ - ArN2CO2. For example, compound 18 shows in its EIMS spectra fragment peaks at m/z
505 and 489, arising from the loss of ClC6H4N2CO and ClC6H4N2CO2, respectively. This type of
fragmentation was previously observed with analogous spiro compounds[8,9].
Finally, it is worth mentioning here that although the formation of the 4-methylene-naphthoxazines
9-16 would be expected to proceed via a similar reaction mechanism to that previously reported for the
cyclization of hydrazones of 2-hydroxyacetophenone and acetophenone [6,10], the mechanism for
formation of the spiro naphthoxazine dimmers is not clear to us with regards to at what stage does the
dimerization occurs to form the final spiro naphthoxazines.
Scheme 4. Proposed mechanism for the formation of the spiro compounds 17-20.
NHAr
H3C
N
OH
(Cl3CO)2CO
NHAr
N
NHAr
N
NHAr
N
H3C
H3C
H
H2C
O
C
O
Cl
O
C
O
Cl
O
C
O
Cl
-Cl
-Cl
NHAr
NHAr
NHAr
N
H3C
N
O
H2C
N
O
H
H2C
O
O
O
O
-H
O
O
O
O
ArHN
N
ArHN
N
-H
N
O
Ar
O
NHAr
N
H3C
O
N
H3C
O

Molecules 2009, 14
2153
Scheme 4. Cont.
H3C
N
NHAr
OH
H2C
NH NHAr
OH
HO
ArHN
N
NHAr
N
H2C
NH NHAr
OH
H3C
O
NHAr
N
O
-H
H3C
O
+
O
(Cl3CO)2CO
Cl
O
O
O
ArHN
O
ArHN
N
N
NHAr
N
NHAr
N
-Cl
H3C
O
H3C
O
O
O
-H
O
O
ArHN
N
N
Ar
O
N
H3C
O
The use of 1.0 equivalents of triphosgene is necessary to form the latter products because in its
reactions it gives an equivalent of three moles of phosgene (COCl2), so the formation of
naphthoxazines (where one CO group is introduced) would require only 0.5 equivalent of triphosgene
(1.5 equivalent of COCl2, a slight excess is usually used in these kinds of cyclizations) while the spiro
dimers (where two CO groups are introduced) would require double this amount. In Scheme 4, a
speculative mechanism for the formation of the spiro products is shown with two pathways; in the first
one the dimerization occurs after the formation of the two naphthoxazine nuclei, while in the second
one the dimerization takes place before the formation of the second naphthoxazine ring.

Molecules 2009, 14
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Experimental
Melting points are uncorrected. IR spectra were recorded on a Perkin-Elmer 883 spectrophotometer
as KBr pellets and expressed as  in cm-1. NMR spectra were recorded on JEOL ECP 400 (400 MHz)
in CDCl3 and chemical shifts are expressed as  in ppm. MS spectra were recorded on Shimadzu QP
5050A GC/MS system.
2-Acetyl-1-naphthol phenylhydrazone (1): To a solution of 2-acetyl-1-naphthol (2.0 g, 10.8 mmol) in
ethanol (50 mL) was added a solution of phenylhydrazine hydrochloride (1.9 g, 12.9 mmol) and
sodium acetate (1.0 g, 12.2 mmol) in a mixture of ethanol (30 mL) and water (10 mL). The above
solution was refluxed for 5 hours and then evaporated under vacuum. The resulting solid was washed
with water (50 mL) and then recrystallized from ethanol-chloroform (8:2). Yield 92%, red solid, mp
1
162C; IR: 3,410 (OH), 3,334 (NH), 1,620 (C=N); H-NMR: 1.81 (s, 3H), 6.17 (t, J = 7.3 Hz, 1H),
6.46 (d, J = 7.7 Hz, 2H), 6.62 (m, 3H), 6.77 (m, 2H), 6.88 (d, J = 8.8 Hz, 1H), 7.06 (m, 1H),
7.64 (m, 1H); 13C-NMR: 13.04, 112.42, 114.49, 117.42, 119.49, 122.49, 123.58, 124.66, 126.51,
126.75, 128.60, 128.84, 133.41, 144.69, 148.03, 154.09; MS: m/z (%) 276 (M+, 100), 261 (7),
260 (18), 295 (38), 230 (6), 183 (25), 168 (6), 141 (13), 128 (10), 115 (49), 77 (8); Anal. Calcd. for
C18H16N2O: C, 78.23; H, 5.83; N, 10.13. Found: C, 77.96; H, 5.71; N, 10.28.
2-Acetyl-1-naphthol 4-̀ chlorophenylhydrazone (2): This compound was prepared from 2-acetyl-1-
naphthol and 4-chlorophenylhydrazine using the procedure described for 1. Yield, 82%, brownish
̀
solid, mp 175C; IR: 3,420 (OH), 3,331 (NH), 1,636 (C=N); 1H-NMR: 2.38 (s, 3H),
6.98 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.32 (m, 2H), 7.49 (m, 2H), 7.73 (m, 1H), 8.40 (m,
1H); 13C-NMR: 12.28, 112.67, 114.27, 118.24, 123.22, 123.51, 125.37, 125.67, 127.15, 127.34,
129.49, 134.28, 142.68, 149.27, 155.67; MS: m/z (%) 312 (M+2, 21), 310 (M+, 65), 296 (5), 294 (10),
293 (51), 258 (17), 184 (30), 183 (41), 169 (10), 168 (9), 143 (22), 141 (25), 134 (45), 127 (100), 114
(37), 76 (6); Anal. Calcd. for C18H15ClN2O: C, 69.56; H, 4.86; N, 9.01. Found: C, 69.72; H, 4.77; 8.88.
2-Acetyl-1-naphthol 4-̀ bromophenylhydrazone (3): This compound was prepared from 2-acetyl-1-
naphthol and 4-bromophenylhydrazine using the procedure described for 1. Yield, 79%, brownish
̀
solid, mp 182C; IR: 3,412 (OH), 3,348 (NH), 1,632 (C=N); 1H-NMR: 2.40 (s, 3H),
6.94 (d, J= 8.1 Hz, 2H), 7.31 (d, J= 8.8 Hz, 1H), 7.41 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.1 Hz, 2H),
13
7.53 (m, 2H), 7.74 (m, 1H), 8.41 (m, 1H); C-NMR: 12.29, 112.92, 113.20, 118.20, 121.12, 123.32,
123.63, 125.33, 125.38, 127.23, 127.30, 129.70, 134.27, 144.11, 148.52, 155.12; MS: m/z (%) 356
(M+2, 70), 354 (M+, 71), 340 (11), 339 (54), 338 (12), 337 (49), 258 (21), 185 (15), 183 (56), 173
(63), 156 (10), 128 (18), 115 (100), 91 (35), 76 (6); Anal. Calcd. for C18H15BrN2O: C, 60.86; H, 4.25;
N, 7.88. Found: C, 60.67; H, 4.15; N, 7.75.
2-Acetyl-1-naphthol 4-̀ methylphenylhydrazone (4): This compound was prepared from 2-acetyl-1-
naphthol and 4-methylphenylhydrazene using the procedure described for 1. Yield, 91% brownish
̀
solid, mp 164C; IR: 3,424 (OH), 3,350 (NH), 1,614 (C=N); 1H-NMR: 2.01 (s, 3H), 2.19 (s, 3H), 6.76
(d, J = 8.1 Hz, 2H), 6.80 (d, J = 8.1 Hz, 2H), 7.02 (m, 1H), 7.17 (m, 2H), 7.24 (m, 1H), 7.45 (m, 1H),
8.06 (m, 1H); 13C-NMR: 12.22, 20.73, 113.03, 113.31, 118.13, 118.42, 123.31, 123.62, 125.01,

Molecules 2009, 14
2155
125.32, 127.22, 127.49, 130.15, 134.21, 141.96, 148.05, 155.06; MS: m/z (%) 290 (M+, 85), 275 (14),
273 (54), 185 (15), 168 (12), 128 (6), 115 (37), 107 (100), 93 (6), 76 (25); Anal. Calcd. for
C19H18N2O: C, 78.59; H, 7.95; N, 12.27. Found: C, 78.38; H, 7.85; N, 12.12.
1-Acetyl-2-naphthol phenylhydrazone (5): This compound was prepared from 1-acetyl-2-naphthol and
phenylhydrazine hydrochloride using the procedure described for 1. Yield, 75%, pale yellow solid, mp
125C; IR: 3,418 (OH), 3,335 (NH), 1,617 (C=N); 1H-NMR: 2.49 (s, 3H), 6.93 (t, J= 7.3Hz, 1H), 7.12
(d, J = 7.3 Hz, 2H), 7.21 (d, J = 8.8 Hz, 1H), 7.29 (d, J= 7.3 Hz, 2H), 7.33 (m, 1H), 7.44 (m, 1H), 7.79
(d, J = 8.1 Hz, 1H); 13C-NMR: 18.41, 113.18, 116.32, 118.64, 121.13, 123.15, 124.52, 126.50, 128.97,
129.26, 129.63, 130.77, 131.66, 144.24, 144.76, 153.43; MS: m/z (%) 276 (M+, 69), 260 (21), 259
(100), 184 (22), 169 (6), 141 (9), 128 (7), 115 (28), 93 (33), 77 (9); Anal. Calcd. for C18H16N2O:
C, 78.23, H, 5.73, N, 10.13. Found: C, 78.11; H, 5.73, N, 10.08.
1-Acetyl-2-naphthol 4-̀ chlorophenylhydrazone (6): This compound was prepared from 1-acetyl-2-
naphthol and 4-chlorophenylhydrazine using the procedure described for 1. Yield, 80%, pale yellow
̀
1
solid, mp 154C; IR: 3,422 (OH), 3,355 (NH), 1,619 (C=N); H-NMR: 2.47 (s, 3H), 7.04
(d, J = 9.2 Hz, 2H), 7.21 (d, J = 9.2 Hz, 2H), 7.24 (d, J = 8.8, 1H), 7.33 (m, 1H), 7.44 (m, 1H),
7.66 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.77 (d, J= 7.7 Hz, 1H); 13C-NMR: 18.42, 114.36,
116.29, 118.57, 123.24, 124.44, 126.60, 129.00, 129.05, 129.30, 129.51, 130.94, 131.65, 142.93,
143.11, 153.30; MS: m/z (%) 312 (M+2, 21), 310 (M+, 62), 296 (7), 295 (34), 294 (23), 293 (100), 184
(45), 183 (18), 169 (16), 168 (9), 141 (24), 127 (74), 76 (6); Anal. Calcd. for C18H15ClN2O: C, 69.56;
H, 4.86; N, 9.01. Found: C, 69.42; H, 4.73; N, 9.12.
1-Acetyl-2-naphthol 4-
̀
bromophenylhydrazone (7): This compound was prepared from 1-acetyl-2-
naphthol and 4
̀
mp 153C; IR: 3,436 (OH), 3,354 (NH), 1,619 (C=N); 1H-NMR: 2.49 (s, 3H), 7.01 (d, J = 8.8 Hz, 2H),
7.24 (d, J = 8.4 Hz, 1H), 7.34 (m, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.45 (m, 1H), 7.67 (d, J = 8.4 Hz, 1H),
13
7.73 (d, J = 8.8 Hz, 1H), 7.78(d, J = 8.4 Hz, 1H); C-NMR: 18.29, 112.86, 114.66, 116.23, 118.48,
123.14, 124.35, 126.49, 128.90, 129.20, 130.82, 131.54, 132.31, 143.29, 145.04, 153.19; MS: m/z (%)
356 (M+2, 71), 354 (M+, 75), 340 (19), 339 (97), 338 (22), 337 (100), 258 (8), 210 (17), 185 (12), 183
(27), 173 (44), 169 (67), 115 (87), 76 (7); Anal. Calcd. for C18H15BrN2O: C, 60.86; H, 4.25; N, 7.88.
Found: C, 60.73; H, 4.38; N, 7.93.
1-Acetyl-2-naphthol 4-̀ methylphenylhydrazone (8): This compound was prepared from 1-acetyl-2-
naphthol and 4-methylphenylhydrazine using the procedure described for 1. Yield, 68%, yellow solid,
̀
1
mp 132 C; IR: 3,417 (OH), 3,360 (NH), 1,618 (C=N); H-NMR: 2.29 (s, 3H), 2.49 (s, 3H),
7.02 (d, J= 8.1 Hz, 2H), 7.09 (d, J= 8.1 Hz, 2H), 7.21 (d, J= 8.8 Hz, 1H), 7.32 (m, 1H), 7.44 (m, 1H),
13
7.68 (d, J= 8.1 Hz, 1H), 7.72 (d, J= 8.8 Hz, 1H), 7.78 (d, J= 7.3 Hz, 1H); C-NMR: 18.55, 20.69,
113.38, 116.22, 118.66, 123.15, 124.51, 126.51, 128.96, 129.24, 130.09, 130.62, 130.81, 131.65,
142.05, 143.11, 153.54; MS: m/z (%) 290 (M+, 89), 273 (100), 184 (30), 169 (7), 141 (11), 128 (8),
115 (35), 107 (57), 106 (36), 105 (46), 91 (6), 76 (25); Anal. Calcd. for C19H18N2O: C, 78.59; H, 7.95;
N, 12.27. Found: C, 78.41; H, 7.81; N, 12.18.

Molecules 2009, 14
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4-Methylene-3-(N-phenylamino)-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one (9): To a stirred
solution of 0.20 g (0.72 mmol) of 1 and triethylamine (1 mL) in dichloromethane (30 mL) was added
dropwise under N2 atmosphere a solution of 0.5 equivalent (0.12 g, 0.36 mmol) of triphosgene in
dichloromethane (10 mL). The mixture was refluxed for 4 hours and then washed with water. The
organic layer was dried over magnesium sulfate and evaporated under vacuum. The resulting solid was
recrystallized from a mixture of benzene-ethanol (1:1). Yield, 69%, colorless solid, mp 196C; IR:
3,306 (NH), 1,727 (C=O), 1,620 (=CH2); 1H-NMR: 5.02 (d, J = 2.2 Hz, 1H), 5.13 (d, J = 2.2 Hz, 1H),
6.80 (d, J = 8.1 Hz, 2H), 7.02 (m, 3H), 7.55 (m, 2H), 7.61 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H),
13
7.83 (m, 1H), 8.20 (m, 1H), 8.33 (bs, 1H); C-NMR: 88.60, 111.50, 113.03, 120.69, 121.57, 122.93,
125.18, 127.46, 127.89, 128.12, 128.60, 129.30, 134.57, 138.69, 143.05, 146.16, 148.05; MS: m/z (%)
302 (M+, 13), 260 (25), 259 (100), 232 (11), 230 (23), 182 (18), 168 (11), 140 (9), 139 (17), 128 (25),
92 (13), 77 (9); Anal. Calcd. for C19H14N2O2: C, 75.48; H, 4.67; N, 9.27. Found: C, 75.13; H, 4.50;
N, 9.63.
4-Methylene-3-[N-(4
̀
-chlorophenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one
(10):
Prepared from 2 and triphosgene using the procedure described for 9. Yield, 74%, pale yellow solid,
mp 182C; IR: 3,260 (NH), 1,732 (C=O), 1,621 (=CH2); 1H-NMR: 5.02 (d, J = 2.2 Hz, 1H), 5.09 (d, J
= 2.2 Hz, 1H), 6.57 (bs, 1H), 6.78 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 7.59 (m, 3H), 7.67 (d,
J = 8.8 Hz, 1H), 7.85 (m, 1H), 8.30 (m, 1H); 13C-NMR: 88.55, 111.09, 114.46, 115.70, 120.24, 121.48,
123.03, 125.36, 127.53, 127.70, 128.22, 132.33, 134.68, 138.26, 143.46, 144.45, 147.99; MS: m/z (%)
338 (M+2, 6), 336 (M+, 17), 301 (24), 296 (9), 295 (32), 294 (23), 293 (91), 259 (28), 258 (100), 230
(17), 182 (53), 140 (18), 128 (74), 115 (21), 98 (31), 76 (10); Anal. Calcd. for C19H13Cl N2O2:
C, 67.76; H, 3.89; N, 8.31. Found: C, 67.47; H, 3.71; N, 8.19.
4-Methylene-3-[N-(4
̀
-bromophenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one
(11):
Obtained from 3 and triphosgene using the procedure described for 9. Yield, 71%, brownish solid, mp
1
185C; IR: 3,281 (NH), 1,741 (C=O), 1,621 (=CH2); H-NMR: 4.96 (d, J = 2.0 Hz, 1H),
5.01 (d, J = 2.0 Hz, 1H), 6.73 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.54 (m, 4H), 7.83 (m, 1H),
8.17 (m, 1H), 8.69 (bs, 1H); 13C-NMR: 88.58, 111.33, 112.06, 114.89, 120.73, 121.52, 122.88, 125.27,
127.53, 127.95, 128.21, 131.99, 134.59, 138.54, 143.35, 145.60, 147.35; MS: m/z (%) 382 (M+2, 12),
380 (M+, 13), 354 (12), 340 (16), 339 (74), 337 (72), 301 (44), 259 (36), 258 (100), 230 (26), 182 (58),
128 (74), 115 (33), 91 (43), 76 (11); Anal. Calcd. for C19H13BrN2O2: C, 59.86; H, 3.43; N, 7.34.
Found: C, 59.73; H, 3.33; N, 7.43.
4-Methylene-3-[N-(4-methylphenyl)amino]-3,4-dihydro-2H-naphth[2,1-e]-1,3-oxazine-2-one
(12):
Obtained from 4 and triphosgene using the procedure described for 9. Yield, 73%, brownish solid, mp
150C; IR: 3,260 (NH), 1,737 (C=O), 1,612 (=CH2); 1H-NMR: 2.19 (s, 3H), 4.92 (d, J = 2.0 Hz, 1H),
5.14 (d, J = 2.0 Hz, 1H), 6.71 (d, J = 8.1 Hz, 2H), 7.02 (d, J = 8.1 Hz, 2H), 7.69 (m, 2H),
7.84 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 8.8 Hz, 1H), 8.04 (m, 1H), 8.17 (m, 1H), 8.67 (bs, 1H);
13C-NMR: 20.72, 88.97, 111.70, 113.07, 121.50, 122.80, 125.43, 128.10, 128.43, 128.62, 129.14,
130.03, 134.66, 138.99, 143.34, 144.14, 147.21; MS: m/z (%) 316 (M+, 24), 274 (20), 273 (100), 244

Molecules 2009, 14
2157
(10), 182 (13), 128 (23), 105 (61), 76 (31); Anal. Calcd. for C20H16N2O2: C, 75.93; H, 5.10; N, 8.85.
Found: C, 75.81; H, 5.15; N, 8.77.
4-Methylene-3-(N-phenylamino)-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one (13): Obtained
from 5 and triphosgene using the procedure described for 9. Yield, 62%, colorless solid, mp 166 C;
1
IR: 3,297 (NH), 1,725 (C=O), 1,620 (=CH2); H-NMR: 5.04 (d, J = 2.2 Hz, 1H), 5.15 (d, J = 2.2 Hz,
1H), 6.53 (bs, 1H), 6.97 (d, J = 8.8 Hz, 2H), 7.25 (m, 3H), 7.58 (m, 3H), 7.67 (d, J = 8.1 Hz, 1H), 7.84
13
(m, 1H), 8.32 (m, 1H); C-NMR: 88.53, 111.24, 113.97, 120.33, 121.90, 122.27, 123.10, 125.23,
127.44, 127.67, 128.12, 129.45, 134.66, 138.46, 143.53, 145.29, 148.07; MS: m/z (%) 302 (M+, 7),
258 (100), 182 (16), 128 (5), 115 (7), 92 (5), 77 (6); Anal. Calcd. for C19H14N2O2 : C, 75.48; H, 4.67;
N, 9.27. Found: C, 75.24; H, 4.71; N, 9.18.
4-Methylene-3-[N-(4-chlorophenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one
(14):
Obtained from 6 and triphosgene using the procedure described for 9. Yield, 61%, brownish solid, mp
1
187C; IR: 3,260 (NH), 1,732 (C=O), 1,620 (=CH2); H-NMR: 5.05 (d, J = 1.5 Hz, 1H),
5.15 (d, J = 1.5 Hz, 1H), 6.52 (bs, 1H), 6.84 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H),
7.51 (m, 3H), 7.70 (d, J = 8.1 Hz, 1H), 7.86 (m, 1H), 8.31 (m, 1H); 13C-NMR: 88.53, 111.10, 115.33,
120.25, 121.87, 123.04, 125.37, 127.22, 127.54, 127.71, 128.23, 129.44, 134.69, 138.30, 143.48,
143.95, 148.01; MS: m/z (%) 338 (M+2, 5), 336 (M+, 14), 301 (24), 295 (29), 259 (29), 258 (100), 230
(14), 182 (60), 128 (68), 115 (21), 99 (36), 76 (9); Anal. Calcd. for C19H13Cl N2O2: C, 67.76; H, 3.89;
N, 8.32. Found: C, 67.59; H, 3.95; N, 8.25.
4-Methylene-3-[N-(4-bromophenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one
(15):
Obtained from 7 and triphosgene using the procedure described for 9. Yield, 64%, colorless solid, mp
1
203C; IR: 3,353 (NH), 1,733 (C=O), 1,616 (=CH2); H-NMR: 5.05 (d, J = 2.2 Hz, 1H),
5.14 (d, J = 2.2 Hz, 1H), 6.53 (bs, 1H), 6.90 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.60 (m,
13
3H), 7.72 (d, J = 8.8 Hz, 1H), 7.82 (m, 1H), 8.12 (m, 1H); C-NMR: 88.54, 111.24, 113.96, 116.78,
120.33, 121.90, 125.24, 127.16, 127.45, 127.68, 128.13, 129.47, 134.66, 138.45, 143.53, 145.29,
148.08; MS: m/z (%) 382 (M+2, 18), 380 (M+, 16), 301 (35), 259 (30), 258 (100), 230 (35), 210 (18),
184 (49), 182 (48), 139 (45), 126 (69), 115 (72), 101 (35), 76 (19); Anal. Calcd. for C19H13BrN2O2:
C, 59.86; H, 3.44; N, 7.35. Found: C, 59.98; H, 3.18; N, 7.12.
4-Methylene-3-[N-(4-methylphenyl)amino]-3,4-dihydro-2H-naphth[1,2-e]-1,3-oxazine-2-one
(16):
Obtained from 8 and triphosgene using the procedure described for 9. Yield 60%, yellowish solid, mp
160C; IR: 3,245 (NH), 1,741 (C=O), 1,615 (=CH2); 1H-NMR: 2.26 (s, 3H), 5.04 (d, J = 2.20 Hz, 1H),
5.14 (d, J = 2.20 Hz, 1H), 6.47 (bs, 1H), 6.81 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 7.58 (m,
13
3H), 7.66 (d, J = 8.8 Hz, 1H), 7.85 (m, 1H), 8.32 (m, 1H); C-NMR: 20.71, 88.50, 111.28, 114.12,
120.34, 121.91, 123.10, 125.19, 127.43, 127.67, 128.10, 129.96, 131.73, 134.63, 138.48, 142.88,
143.53, 148.10; MS: m/z (%) 316 (M+, 13) 274 (17), 273 (100), 182 (11), 139 (15), 128 (20), 106 (52),
76 (36); Anal. Calcd. for C20H16N2O2: C, 75.93; H, 5.10; N, 8.85. Found: C, 75.75; H, 5.22; N, 8.73.

Molecules 2009, 14
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3’-Phenyl-3-(phenylamino)-1’,12’b-dihydro-12`b-methylspiro{4H-naphth[2,1-e]-1,3-oxazine-4,2’
(3’H)- [5H]pyrazolo[1,5-c]naphth[2,1-e]-1,3-oxazine}-2,5’-dione (17): Obtained from 1 and one
equivalent of triphosgene using the procedure described for 9. Yield 69%, reddish solid, mp 207 C;
1
IR: 3,256 (NH), 1,748, 1,755 (2C=O); H-NMR: 2.12 (s, 3H), 3.58 (d, J = 14.70 Hz, 1H),
3.65 (d, J = 14.70 Hz, 1H), 6.72 (m, 4H), 6.97 (m, 4H), 7.11 (m, 5H), 7.58 (m, 5H), 7.91 (m, 2H), 8.40
(m, 2H); 13C-NMR: 32.15, 59.65, 66.06, 85.55, 112.48, 112.93, 113.91, 116.47, 116.80, 119.92,
120.36, 121.68, 122.19, 122.23, 124.96, 125.49, 127.55, 127.68, 128.81, 129.19, 133.56, 133.86,
134.09, 141.92, 142.46, 142.78, 143.18, 145.29, 145.42, 145.69, 149.24, 149.90; MS: m/z (%) 471
(M+ - C6H5N2CO, 20), 455 (M+ - C6H5N2CO2, 14), 440 (57), 423 (28), 351 (12), 302 (21), 259 (100),
258 (17), 230 (34), 185 (29), 168 (39), 128 (21), 115 (38), 93 (70), 77 (51), 63 (35); Anal. Calcd. for
C38H28N4O4: C, 75.48; H, 4.66; N, 9.26. Found: C, 75.21; H, 4.71; N, 9.19.
3’-(4-Chlorophenyl)-3-[(4-chlorophenyl)amino]-1’,12’b-dihydro-12’-b-methylspiro{4H-naphth[1,2-
e]-1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,5-c]naphth[2,1-e]-1,3-oxazine}-2,5’-dione
(18):
This
compound was obtained from 2 and one equivalent of triphosgene using the procedure described for 9.
1
Yield, 72%, mp 267C; IR: 3,219 (NH), 1,724, 1,753 (2C=O); H-NMR: 2.10 (s, 3H),
3.49 (d, J = 14.70 Hz, 1H), 3.60 (d, J = 14.70 Hz, 1H), 6.35 (m, 3H), 6.65 (m, 4H), 6.93 (m, 4H), 7.66
13
(m, 5H), 7.82 (m, 2H), 8.40 (m, 2H); C-NMR: 32.08, 60.07, 66.05, 85.47, 111.88, 114.22, 117.91,
119.62, 121.02, 121.54, 122.16, 122.56, 123.11, 125.25, 125.57, 126.45, 127.18, 127.40, 127.47,
127.66, 127.78, 127.93, 128.81, 128.84, 128.91, 133.47, 134.31, 141.39, 141.81, 143.90, 145.61,
149.61, 149.01, 149.07; MS: m/z (%) 505 (M+- ClC6H4N2CO, 22), 489 (M+- ClC6H4N2CO2, 100),
410 (7), 336 (13), 295 (12), 259 (21), 230 (10), 168 (26), 139 (24), 127 (28), 115 (21), 99 (9), 90 (5),
76 (15), 63 (12); Anal. Calcd. for C38H26Cl2N4O4: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.46; H,
3.68; N, 8.54.
3’-(4-Bromophenyl)-3-[(4-bromophenyl)amino]-1’,12’b-dihydro-12’b-methylspiro{4H-naphth[2,1-e]-
1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,5-e]naphth[2,1-e]-1,3-oxazine}-2,5’-dione
(19): Obtained
from 3 and one equivalent of triphosgene using the procedure described for 9. Yield, 71%, mp 246 C;
1
IR: 3,232 (NH), 1,730, 1,745 (2C=O); H-NMR: 2.09 (s, 3H), 3.44 (d, J = 14.70 Hz, 1H),
3.54 (d, J = 14.70 Hz, 1H), 6.28 (m, 3H), 6.60 (m, 3H), 6.85 (m, 2H), 7.04 (m, 2H), 7.52 (m, 6H),
13
7.78 (m, 2H), 8.34 (m, 2H); C-NMR: 32.04, 60.11, 65.96, 85.41, 111.75, 113.97, 114.67, 115.87,
117.98, 118.21, 119.56, 121.00, 121.53, 122.16, 122.55, 123.11, 125.31, 127.42, 127.48, 127.69,
127.79, 127.95, 128.94, 131.70, 131.74, 132.05, 133.66, 134.31, 141.78, 141.88, 144.40, 148.95,
149.15; MS: m/z (%) 549 (M+- BrC6H4N2CO, 6), 533 (M+- BrC6H4N2CO2, 100), 409 (15), 382 (20),
380 (17), 340 (24), 339 (85), 258 (86), 202 (24), 196 (51), 168 (74), 129 (59), 115 (84), 99 (51), 91
(49), 90 (52), 76 (71), 63 (84); Anal. Calcd. for C38H26Br2N4O4: C, 59.86; H, 3.43; N, 7.34. Found: C,
59.73; H, 3.49; N, 7.42.
3’-(4-Chlorophenyl)-3-[(4-chlorophenyl)amino]-1’,12’b-dihydro-12’b-methylspiro{4H-naphth[1,2-e]-
1,3-oxazine-4,2’(3’H)-[5H]pyrazolo[1,54-c]naphth[1,2-e]-1,3-oxazine}-2,5’-dione (20): Obtained
from 6 and one equivalent of triphosgene using the procedure described for 9. Yield, 55%; mp 227 C;
1
IR: 3,338 (NH), 1,730, 1,755 (2C=O); H-NMR: 2.51 (s, 3H), 3.41 (d, J = 14.65 Hz, 1H),

Molecules 2009, 14
2159
3.54 (d, J = 14.65 Hz, 1H), 7.07 (m, 3H), 7.25 (m, 4H), 7.51 (m, 5H), 8.11 (m, 4H), 8.29 (m, 2H),
13
8.61 (m, 2H); C-NMR: 17.20, 27.87, 88.06, 97.68, 114.00, 114.31, 114.46, 115.89, 116.26, 120.55,
123.56, 124.20, 124.87, 125.67, 125.73, 127.89, 128.57, 128.72, 128.87, 128.93, 129.76, 131.21,
131.32, 131.66, 131.77, 131.80, 136.60, 138.88, 143.81, 144.17, 145.50, 147.04, 148.60, 149.01; MS:
m/z (%) 505 (M+- ClC6H4N2CO, 20), 489 (M+- ClC6H4N2CO2, 100), 410 (7), 336 (21), 319 (15), 295
(21), 293 (44), 258 (31), 230 (14), 139 (29), 127 (44), 115 (35), 75 (20), 63 (16); Anal. Calcd. for
C38H26Cl2N4O4: C, 67.76; H, 3.89; N, 8.32. Found: C, 67.53; H, 3.93; N, 8.46.
References
1. Di Santo, R.; Costi, R.; Artico, M.; Massa, S.; Morangiu, M.E.; Loi, A.G.; De Montis, A.; La
Colla, P. 1,2,5-Benzothiadiazepine and pyrrolo[2,1d][1,2,5]benzothiadiazepine derivatives with
specific anti-human immunodeficiency virus type 1 activity. Antiviral Chem. Chemother. 1998, 9,
127.
2. Chung, Y.J.; Jung, Y.S.; Seong, C.M.; Park, N.S. An Efficient Synthesis of 3-Substituted
Quinazolones. Bull. Korean Chem. Soc. 1998, 19, 1117.
3. Nefzi, A.; Otresh, J.M.; Giulianotti, M.; Hougten, R.A. Efficient solid phase synthesis of 3,5-
disubstituted hydantoins. Tetrahedron Lett. 1998, 39, 8199.
4. Li, Z.; Zhang, Y. Low-valent titanium induced cyclization of dimeric dianions of anils with
triphosgene: a safe and efficient method for the syntheses of substituted imidazolidine 2-ones.
Synth. Commun. 2002, 32, 2613.
5. Krishnaswamy, D.; Govande,V.V.; Gumaste, V.K.; Bhawal, B.M.; Deshmukh, A.R.A.S.
Triphosgene: a versatile reagent for the synthesis of azetidin-2-ones. Tetrahedron 2002, 58, 2215.
6. Alkhathlan, H.Z. Synthesis of 4-alkoxy-4-methyl- and 4-alkoxy-4-fluoromethyl-1,3-
benzoxazinones. Tetrahedron 2003, 59, 8163.
7. Alkhathlan, H.Z. A One-Pot Synthesis of 1,3-Benzoxazines. Synth. Commun. 2004, 34, 71.
8. Alkhathlan, H.Z.; Al-Saad, M.A.; Al-Hazimi, H.M.; Al-Farhan, K.A.; Mousa, A.A. Synthesis and
X-ray crystal structures of novel spiro 1,3-benzoxazine dimmers. J. Chem. Res. 2002,
(S) 473, (M) 1023.
9. Alkhathlan, H.Z.; Al-Saad, M.A.; Al-Hazimi, H.M.; Al-Farhan, K.A.; Mousa, A.A. Quinazoline,
pyrazolo[1,5-c]quinazoline and spiro quinazoline dimers from the reaction of 2-
aminoacetophenone hydrazones with triphosgene. J. Chem. Res. 2002, (S) 587, (M) 1201.
10. Molina, P.; Conesa, C.; Alias, A.; Arques, A.; Velasco, M. Preparation and synthetic applications
of iminophosphoranes derived from o-substituted arylazides: preparation of pyrazolo [1,2-b]
indazole,
4H-3,1-benzoxazine
and
quinoline
derivatives.
Crystal
structure
of
2-[2-(4-methoxybenzoylamino)phenyl]-4-methylquinoline. Tetrahedron 1993, 49, 7599.
Sample Availability: Samples of the compounds are available from the authors.
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
This article is an open-access article distributed under the terms and conditions of the Creative
Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).